Persistence of abnormalities in white matter in children with type 1 diabetes

• Published in: Diabetologia Vol. 61; no. 7; pp. 1538 - 1547
• Main Authors: Fox, Larry A., Hershey, Tamara, Mauras, Nelly, Arbeláez, Ana Maria, Tamborlane, William V., Buckingham, Bruce, Tsalikian, Eva, Englert, Kim, Raman, Mira, Jo, Booil, Shen, Hanyang, Reiss, Allan, Mazaika, Paul
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-07-2018; Springer Nature B.V
• Subjects: Age Factors; Anisotropy; Attention deficit hyperactivity disorder; Biomarkers - blood; Blood Glucose - metabolism; Case-Control Studies; Child; Child Development; Child, Preschool; Children; Cognitive ability; Cognitive Dysfunction - etiology; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - diagnosis; Diffusion Tensor Imaging; Female; Glucose monitoring; Glycated Hemoglobin A - metabolism; Human Physiology; Humans; Hyperglycemia; Internal Medicine; Leukoencephalopathies - diagnostic imaging; Leukoencephalopathies - etiology; Leukoencephalopathies - physiopathology; Longitudinal Studies; Magnetic Resonance Imaging; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Neurological disorders; Pediatrics; Prognosis; Risk Factors; Substantia alba; Time Factors; United States; Paediatric diabetes; White matter; Brain development
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-018-4610-6

Aims/hypothesis
Prior studies suggest white matter growth is reduced and white matter microstructure is altered in the brains of young children with type 1 diabetes when compared with brains of non-diabetic children, due in part to adverse effects of hyperglycaemia. This longitudinal observational study examines whether dysglycaemia alters the developmental trajectory of white matter microstructure over time in young children with type 1 diabetes.
Methods
One hundred and eighteen children, aged 4 to <10 years old with type 1 diabetes and 58 age-matched, non-diabetic children were studied at baseline and 18 months, at five Diabetes Research in Children Network clinical centres. We analysed longitudinal trajectories of white matter using diffusion tensor imaging. Continuous glucose monitoring profiles and HbA
1c
levels were obtained every 3 months.
Results
Axial diffusivity was lower in children with diabetes at baseline (
p
 = 0.022) and at 18 months (
p
 = 0.015), indicating that differences in white matter microstructure persist over time in children with diabetes. Within the diabetes group, lower exposure to hyperglycaemia, averaged over the time since diagnosis, was associated with higher fractional anisotropy (
p
 = 0.037). Fractional anisotropy was positively correlated with performance (
p
 < 0.002) and full-scale IQ (
p
 < 0.02).
Conclusions/interpretation
These results suggest that hyperglycaemia is associated with altered white matter development, which may contribute to the mild cognitive deficits in this population.